Spontaneous cSCC Murine Model Shows Limited Response to PD-1 Blockade and Radiation Combination Therapy

Area of Science:

• Oncology
• Immunology
• Preclinical Research

Background:

• Cutaneous squamous cell carcinoma (cSCC) is a prevalent non-melanoma skin cancer with significant morbidity.
• Advanced cSCC necessitates multimodality therapy due to poor prognosis and high recurrence rates.
• Limited data exists on preclinical models combining immunotherapy and radiation for cSCC.

Purpose of the Study:

• To evaluate the efficacy of combining anti-PD1 antibody therapy with localized radiation in a preclinical cSCC model.
• To investigate the impact of this combination therapy on tumor growth and immune cell infiltration.
• To establish a model for studying resistance mechanisms to immunotherapy in cSCC.

Main Methods:

• DMBA/TPA induced tumors in mice were treated for three weeks.
• Treatment groups included IgG control, anti-PD1 monotherapy, 8 Gy radiation, and combination therapy.
• Tumor growth and histological changes, including CD8+ T cell infiltration, were analyzed.

Main Results:

• Anti-PD1 monotherapy showed a non-significant trend toward slowed tumor growth (p=0.0775).
• Combination therapy enhanced CD8+ T cell infiltration but increased variability.
• Histological analysis revealed fibroblastic spindle-like morphology in irradiated tumors.

Conclusions:

• The tested combination therapy did not significantly control cSCC tumor growth in this model.
• This preclinical model is valuable for investigating mechanisms of immunotherapy resistance in cSCC.
• Further research is needed to optimize combination strategies for advanced cSCC.